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Endothelin Receptor Antagonist — Pulmonary Arterial Hypertension Pregnancy: ABSOLUTE CONTRAINDICATION — teratogenic; mandatory Pregnancy Prevention Programme; two forms of contraception required

Bosentan

Brand names: Tracleer

Adult dose

Dose: 62.5 mg twice daily × 4 weeks (initiation), then 125 mg twice daily (maintenance)
Route: Oral
Frequency: Twice daily (morning and evening)
Max: 125 mg twice daily
Dual endothelin receptor antagonist (ERA — ETA and ETB) for PAH (WHO Group 1) — blocks endothelin-1 vasoconstrictive and proliferative effects in pulmonary vasculature. Reduces pulmonary vascular resistance. Regular LFT monitoring mandatory.

Paediatric dose

Dose: 2 mg/kg twice daily (starting dose) mg/kg
Route: Oral
Frequency: Twice daily
Max: 62.5 mg twice daily (children — do not increase to adult dose)
BNFc: licensed from 3 years of age. Dispersible tablet formulation (Tracleer 32 mg dispersible) for children. Specialist paediatric cardiology/respiratory input required.

Dose adjustments

Renal

No dose adjustment required

Hepatic

Contraindicated in moderate-severe hepatic impairment (Child-Pugh B or C); dose reduction in mild impairment

Paediatric weight-based calculator

BNFc: licensed from 3 years of age. Dispersible tablet formulation (Tracleer 32 mg dispersible) for children. Specialist paediatric cardiology/respiratory input required.

Clinical pearls

  • BREATHE-1 trial: bosentan improved 6MWD by 36 metres and reduced clinical worsening in WHO class III–IV PAH
  • Monthly LFT monitoring is MANDATORY — hepatotoxicity in up to 11% of patients; withhold if AST/ALT >3× ULN, stop permanently if >8× ULN
  • Pregnancy Prevention Programme mandatory — bosentan is teratogenic; two forms of contraception required (hormonal methods may be less reliable due to drug interaction — use barrier method as one form)
  • Enzyme inducer: bosentan induces CYP2C9 and CYP3A4 — reduces efficacy of hormonal contraceptives, warfarin, statins, ciclosporin; check all interactions carefully
  • Haemoglobin monitoring: bosentan causes anaemia (haemodilution and reduced erythropoiesis) — check FBC every 3 months
  • Now largely superseded by macitentan and ambrisentan (fewer interactions, less hepatotoxicity) in newly diagnosed PAH — bosentan retained in paediatrics

Contraindications

  • Moderate-severe hepatic impairment
  • Pregnancy — ABSOLUTE CONTRAINDICATION (teratogenic)
  • Concomitant ciclosporin or glibenclamide (pharmacokinetic interaction)
  • Hypersensitivity to bosentan

Side effects

  • Hepatotoxicity (transaminase elevation — monthly monitoring mandatory)
  • Fluid retention/oedema
  • Anaemia
  • Nasopharyngitis
  • Flushing
  • Headache
  • Teratogenicity

Interactions

  • Ciclosporin — contraindicated (markedly increases bosentan levels via CYP3A4/OATP)
  • Glibenclamide — contraindicated (additive hepatotoxicity + glibenclamide levels reduced)
  • Warfarin — reduces INR (enzyme induction — CYP2C9/CYP3A4 inducer)
  • Hormonal contraceptives — reduced efficacy (enzyme induction); two additional forms of contraception required
  • Simvastatin/atorvastatin — reduce statin levels

Monitoring

  • LFTs monthly
  • FBC every 3 months
  • 6MWD and NT-proBNP
  • Pregnancy test (monthly)
  • ECG and echocardiography

Reference: BNFc; BNF 90; BNFc; BREATHE-1 Trial (Rubin et al. NEJM 2002); ESC/ERS PAH Guidelines 2022; NICE TA127; SPC Tracleer. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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